lncRNA介导的ceRNA调控机制在胰腺癌发生发展中作用的研究进展

doi:10.13481/j.1671-587X.20260533

Abstract

Abstract:

Pancreatic cancer is a gastrointestinal malignant tumor with insidious onset，high malignancy， and extremely poor prognosis. Its clinical treatment faces multiple challenges， such as difficulty in early diagnosis， high metastatic potential， and strong drug resistance. Long non-coding RNAs （lncRNAs） play a key role in the regulation of gene expression in pancreatic cancer through competing endogenous RNA （ceRNA） mechanisms. However， the role and mechanism of lncRNA-mediated ceRNA regulation network in the occurrence and development of pancreatic cancer have not been systematically reviewed， and there is a lack of sufficient theoretical basis for its clinical translation and application prospects. This review summarized recent research advances on the lncRNA-mediated ceRNA regulatory mechanism in the development and progression of pancreatic cancer，systematically summarizing its specific molecular mechanisms in tumor proliferation， metastasis， epithelial-mesenchymal transition（EMT）， tumor microenvironment remodeling， and chemoresistance. It focused on exploring potential therapeutic targets and the derived intervention strategies， and summarized the clinical application value and development prospects of lncRNAs as potential biomarkers. Research on lncRNA-mediated ceRNA regulatory mechanisms is expected to provide new insights for the precise diagnosis and treatment of pancreatic cancer.

Key words: Pancreatic cancer, Long non-coding RNA, Competitive endogenous RNA, Pathogenesis, Tumor progression

CLC Number:

R735.9

Mian QIN,Li YAN,Lu BAI,Shengnan JIA,Xiuyan YU. Research progress in role of lncRNA-mediated ceRNA regulation in development and progression of pancreatic cancer[J].Journal of Jilin University(Medicine Edition), 2026, 52(5): 1512-1519.

References 57

[1]	PARK W， CHAWLA A， O’REILLY E M. Pancreatic cancer： a review［J］. JAMA， 2021， 326（9）： 851-862.
[2]	CASTET F， FABREGAT-FRANCO C， CASTILLO G， et al. Clinical and genomic characterisation of early-onset pancreatic cancer［J］. Eur J Cancer， 2023， 194： 113338.
[3]	WANG S， ZHENG Y， YANG F， et al. The molecular biology of pancreatic adenocarcinoma： translational challenges and clinical perspectives［J］. Signal Transduct Target Ther， 2021， 6（1）： 249.
[4]	HO W J， JAFFEE E M， ZHENG L. The tumour microenvironment in pancreatic cancer： clinical challenges and opportunities［J］. Nat Rev Clin Oncol， 2020， 17（9）： 527-540.
[5]	HALBROOK C J， LYSSIOTIS C A， PASCA DI MAGLIANO M， et al. Pancreatic cancer： advances and challenges［J］. Cell， 2023， 186（8）： 1729-1754.
[6]	刘悦泽，张太平，赵玉沛. 胰腺癌诊治的进展与思考［J］. 临床肝胆病杂志， 2025， 41（4）： 601-604.
[7]	WOOD L D， CANTO M I， JAFFEE E M， et al. Pancreatic cancer： pathogenesis， screening， diagnosis， and treatment［J］. Gastroenterology， 2022， 163（2）： 386-402.
[8]	SHERMAN M H， BEATTY G L. Tumor microenvironment in pancreatic cancer pathogenesis and therapeutic resistance［J］. Annu Rev Pathol， 2023， 18： 123-148.
[9]	REBELO R， XAVIER C P R， GIOVANNETTI E， et al. Fibroblasts in pancreatic cancer： molecular and clinical perspectives［J］. Trends Mol Med， 2023， 29（6）： 439-453.
[10]	SINGHI A D， KOAY E J， CHARI S T， et al. Early detection of pancreatic cancer： opportunities and challenges［J］. Gastroenterology， 2019， 156（7）： 2024-2040.
[11]	BRIDGES M C， DAULAGALA A C， KOURTIDIS A. LNCcation： lncRNA localization and function［J］. J Cell Biol， 2021， 220（2）： e202009045.
[12]	IYER M K， NIKNAFS Y S， MALIK R， et al. The landscape of long noncoding RNAs in the human transcriptome［J］. Nat Genet， 2015， 47（3）： 199-208.
[13]	HERMAN A B， TSITSIPATIS D， GOROSPE M. Integrated lncRNA function upon genomic and epigenomic regulation［J］. Mol Cell， 2022， 82（12）： 2252-2266.
[14]	SLACK F J， CHINNAIYAN A M. The role of non-coding RNAs in oncology［J］. Cell， 2019， 179（5）： 1033-1055.
[15]	XIONG G B， PAN S T， JIN J K， et al. Long noncoding competing endogenous RNA networks in pancreatic cancer［J］. Front Oncol， 2021， 11： 765216.
[16]	WENG W Q， ZHANG Z J， HUANG W G， et al. Identification of a competing endogenous RNA network associated with prognosis of pancreatic adenocarcinoma［J］. Cancer Cell Int， 2020， 20： 231.
[17]	XU J C， XU J， LIU X Y， et al. The role of lncRNA-mediated ceRNA regulatory networks in pancreatic cancer［J］. Cell Death Discov， 2022， 8： 287.
[18]	GONZALES L R， BLOM S， HENRIQUES R， et al. LncRNAs： the art of being influential without protein［J］. Trends Plant Sci， 2024， 29（7）： 770-785.
[19]	KARRETH F A， TAY Y， PERNA D， et al. In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma［J］. Cell， 2011， 147（2）： 382-395.
[20]	SU K， WANG N N， SHAO Q Q， et al. The role of a ceRNA regulatory network based on lncRNA MALAT1 site in cancer progression［J］. Biomed Pharmacother， 2021， 137： 111389.
[21]	ZHANG J H， ZHU H K， LI L J， et al. New mechanism of LncRNA： in addition to act as a ceRNA［J］. Non Coding RNA Res， 2024， 9（4）： 1050-1060.
[22]	MIRZAEI S， ABAD PASKEH M D， HASHEMI F， et al. Long non-coding RNAs as new players in bladder cancer： Lessons from pre-clinical and clinical studies［J］. Life Sci， 2022， 288： 119948.
[23]	ASHRAFIZAVEH S， ASHRAFIZADEH M， ZARRABI A， et al. Long non-coding RNAs in the doxorubicin resistance of cancer cells［J］. Cancer Lett， 2021， 508： 104-114.
[24]	ASHRAFIZADEH M， RABIEE N， KUMAR A P， et al. Long noncoding RNAs （lncRNAs） in pancreatic cancer progression［J］. Drug Discov Today， 2022， 27（8）： 2181-2198.
[25]	ZHANG C P， YU Z Y， YANG S S， et al. ZNF460-mediated circRPPH1 promotes TNBC progression through ITGA5-induced FAK/PI3K/AKT activation in a ceRNA manner［J］. Mol Cancer， 2024， 23（1）： 33.
[26]	ZHOU J， SHI K， HUANG W F， et al. LncRNA RPPH1 acts as a molecular sponge for miR-122 to regulate Wnt1/β-catenin signaling in hepatocellular carcinoma［J］. Int J Med Sci， 2023， 20（1）： 23-34.
[27]	WEI F F， YAN Z Y， ZHANG X M， et al. LncRNA-NEAT1 inhibits the occurrence and development of pancreatic cancer through spongy miR-146b-5p/TRAF6［J］. Biotechnol Genet Eng Rev， 2024， 40（2）： 1094-1112.
[28]	LI T F， ZHAO H B， ZHOU H， et al. LncRNA LINC00857 strengthens the malignancy behaviors of pancreatic adenocarcinoma cells by serving as a competing endogenous RNA for miR-340-5p to upregulate TGFA expression［J］. PLoS One， 2021， 16（3）： e0247817.
[29]	XU J， WANG J， HE Z W， et al. LncRNA CERS6-AS1 promotes proliferation and metastasis through the upregulation of YWHAG and activation of ERK signaling in pancreatic cancer［J］. Cell Death Dis， 2021， 12（7）： 648.
[30]	SANTOS SILVA F， SOUSA C， MENDES A F. Long non-coding RNAs： New perspectives for the diagnosis， prognosis， and treatment of pancreatic cancer［J］. Biochem Pharmacol， 2026， 250： 117933.
[31]	TERASHIMA M， ISHIMURA A， WANNA-UDOM S， et al. MEG8 long noncoding RNA contributes to epigenetic progression of the epithelial-mesenchymal transition of lung and pancreatic cancer cells［J］. J Biol Chem， 2018， 293（47）： 18016-18030.
[32]	JIANG R Q， TANG J W， CHEN Y， et al. The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion［J］. Nat Commun， 2017， 8： 15129.
[33]	LI X J， LAN Q S， LAI W， et al. Exosome-derived lnc-HOXB8-1： 2 induces tumor-associated macrophage infiltration to promote neuroendocrine differentiated colorectal cancer progression by sponging hsa-miR-6825-5p［J］. BMC Cancer， 2022， 22（1）： 928.
[34]	DUTTA A， ROY A， CHATTERJEE S. Long noncoding RNAs in cancer immunity： a new avenue in drug discovery［J］. Drug Discov Today， 2021， 26（1）： 264-272.
[35]	ALSAAB H O. Pathological role of long non-coding （lnc） RNA in the regulation of Wnt/β-catenin signaling pathway during epithelial-mesenchymal transition （EMT）［J］. Pathol Res Pract， 2023， 248： 154566.
[36]	ALDAYYENI H， HJAZI A， SHAHAB S， et al. Functions， mechanisms， and clinical applications of lncRNA LINC00857 in cancer pathogenesis［J］. Hum Cell， 2023， 36（5）： 1656-1671.
[37]	LI Z H， JIANG P， LI J， et al. Tumor-derived exosomal lnc-Sox2ot promotes EMT and stemness by acting as a ceRNA in pancreatic ductal adenocarcinoma［J］. Oncogene， 2018， 37（28）： 3822-3838.
[38]	XIE W K， CHU M， SONG G D， et al. Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer［J］. Semin Cancer Biol， 2022， 83： 303-318.
[39]	YIN Z， ZHOU Y， MA T T， et al. Down-regulated lncRNA SBF2-AS1 in M2 macrophage-derived exosomes elevates miR-122-5p to restrict XIAP， thereby limiting pancreatic cancer development［J］. J Cell Mol Med， 2020， 24（9）： 5028-5038.
[40]	ZHOU C F， YI C H， YI Y X， et al. LncRNA PVT1 promotes gemcitabine resistance of pancreatic cancer via activating Wnt/β-catenin and autophagy pathway through modulating the miR-619-5p/Pygo2 and miR-619-5p/ATG14 axes［J］. Mol Cancer， 2020， 19（1）： 118.
[41]	HUANG Y H， ZHANG R， LYU H， et al. LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance［J］. Int J Biol Sci， 2024， 20（7）： 2698-2726.
[42]	WANG B， YUAN C， QIE Y Y， et al. Long non-coding RNAs and pancreatic cancer： a multifaceted view［J］. Biomed Pharmacother， 2023， 167： 115601.
[43]	GHAFOURI-FARD S， FATHI M， ZHAI T Y， et al. LncRNAs： novel biomarkers for pancreatic cancer［J］. Biomolecules， 2021， 11（11）： 1665.
[44]	HUANG Y Q， ZHANG W， LI Q X， et al. Identification of m6A/m5C/m1A-associated LncRNAs for prognostic assessment and immunotherapy in pancreatic cancer［J］. Sci Rep， 2023， 13（1）： 3661.
[45]	CHEN S Y， DONG J X， LUO X J， et al. Interaction between m6A and ncRNAs and its association with diseases［J］. Cytogenet Genome Res， 2022， 162（4）： 171-187.
[46]	WANG X D， LIU Y， ZHOU M， et al. m6A modified BACE1-AS contributes to liver metastasis and stemness-like properties in colorectal cancer through TUFT1 dependent activation of Wnt signaling［J］. J Exp Clin Cancer Res， 2023， 42（1）： 306.
[47]	TAN F S， CHEN J L， WANG B， et al. LncRNA SBF2-AS1： a budding star in various cancers［J］. Curr Pharm Des， 2022， 28（18）： 1513-1522.
[48]	EL-ASHMAWY N E， AL-ASHMAWY G M， HAMOUDA S M. Long non-coding RNA FAM83H-AS1 as an emerging marker for diagnosis， prognosis and therapeutic targeting of cancer［J］. Cell Biochem Funct， 2021， 39（3）： 350-356.
[49]	WANG Y D， DING X Y， HU H， et al. Long non-coding RNA lnc-PCTST predicts prognosis through inhibiting progression of pancreatic cancer by downregulation of TACC-3［J］. Int J Cancer， 2018， 143（12）： 3143-3154.
[50]	LIN Z J， LU S Y， XIE X B， et al. Noncoding RNAs in drug-resistant pancreatic cancer： a review［J］. Biomed Pharmacother， 2020， 131： 110768.
[51]	LI D R， WENG S T， ZENG K， et al. Long non-coding RNAs and tyrosine kinase-mediated drug resistance in pancreatic cancer［J］. Gene， 2024， 895： 148007.
[52]	JAFARI S， MOTEDAYYEN H， JAVADI P， et al. The roles of lncRNAs and miRNAs in pancreatic cancer： a focus on cancer development and progression and their roles as potential biomarkers［J］. Front Oncol， 2024， 14： 1355064.
[53]	ZHU H， WEI M Y， XU J， et al. PARP inhibitors in pancreatic cancer： molecular mechanisms and clinical applications［J］. Mol Cancer， 2020， 19（1）： 49.
[54]	JIANG P F， YIN Y M， WU Y， et al. Silencing of long non-coding RNA SNHG15 suppresses proliferation， migration and invasion of pancreatic cancer cells by regulating the microRNA-345-5p/RAB27B axis［J］. Exp Ther Med， 2021， 22（5）： 1273.
[55]	LIU Z Q， SHI M X， REN Y Q， et al. Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy［J］. Mol Cancer， 2023， 22（1）： 35.
[56]	YUEN J G， HWANG G R， FESLER A， et al. Development of gemcitabine-modified miRNA mimics as cancer therapeutics for pancreatic ductal adenocarcinoma［J］. Mol Ther Oncol， 2024， 32（1）： 200769.
[57]	FERINO A， MIGLIETTA G， PICCO R， et al. microRNA therapeutics： design of single-stranded miR-216b mimics to target KRAS in pancreatic cancer cells［J］. RNA Biol， 2018， 15（10）： 1273-1285.

Research progress in role of lncRNA-mediated ceRNA regulation in development and progression of pancreatic cancer

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 57

Related Articles 15

Metrics

Comments

Recommended 0

[1]	Yingying ZHANG,Xue WANG,Ningbo XU,Ziqing WU. Bioinformatics analysis of CGGA database based on transcriptome difference in recurrent glioblastoma and its experimental validation [J]. Journal of Jilin University(Medicine Edition), 2026, 52(5): 1408-1419.
[2]	Laiping LI,Guifeng LI,Ruijing DU,Jinzhi PENG,Peixue YAO,Huan JIN. Research progress in biological roles of m⁶A reader protein IGF2BP3 in development and progression of malignant tumor [J]. Journal of Jilin University(Medicine Edition), 2026, 52(5): 1491-1502.
[3]	Xiqian ZHANG,Zhibo DANG,Yunan DU,Pei WU,Hang XIE,Gaofeng TAN. Inhibitory effect of Chaiqi Yigan formula on malignant biological behaviors of liver cancer HepG2 cells by regulating macrophage polarization [J]. Journal of Jilin University(Medicine Edition), 2026, 52(2): 398-409.
[4]	Yu ZHAO,Xiaoshuang HE,Xiaoyin DONG,Fengyi GAO,Jiageng HE. Regulatory effect of lncRNA urothelial carcinoembryonic antigen 1 on anoikis in human gastrointestinal stromal tumor cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2026, 52(2): 429-439.
[5]	Guang YANG,Zhifang ZHENG,Xinhua ZHANG. Research progress in protective effect of miRNA on neonatal hypoxic-ischemic brain injury [J]. Journal of Jilin University(Medicine Edition), 2025, 51(5): 1423-1428.
[6]	Wenxuan LI,Minru ZONG. Research progress in role of migration of Schwann cells in repairment of peripheral nerve injury [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 1137-1144.
[7]	Xiaoshuang HE,Lina XU,Mei CUI,Yu ZHAO,Bei WANG,Zheng HUANG,Yuchao WANG,Wenyan XIN,Chao WU. Effects of lncRNA DUXAP8 in lung cancer A549 cells-derived exosomes on lung cancer cell growth and its mechnism [J]. Journal of Jilin University(Medicine Edition), 2025, 51(4): 958-967.
[8]	Mengyun LU,Yucheng HAN,Yihong HU,Minhui HE,Yanqun ZHANG,Xianqiong ZOU. Effects of glycolipid transfer protein on proliferation, migration，and invasion of pancreatic cancer PANC-1 cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2025, 51(2): 284-295.
[9]	Qingyu HOU,Siyuan YIN,Ji MA,Kunyao PANG,Hongfeng WANG. Research progress in pathogenesis of mild to moderate carpal tunnel syndrome and its nonsurgical treatment methods [J]. Journal of Jilin University(Medicine Edition), 2024, 50(3): 847-853.
[10]	Zhongxin FENG,Mei LI. Effect of soluble CD40 ligand on biological behavior of THP-1 cells through long non-coding RNA linc00239 [J]. Journal of Jilin University(Medicine Edition), 2024, 50(1): 88-96.
[11]	Ruipeng ZHANG,Jie LI. Resistance and regeneration effects of lncRNA GPRC5D-AS1 on muscle atrophy of myocytes in mice induced by dexamethasone and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2023, 49(6): 1457-1465.
[12]	Na NI,Hongliang DONG,Haiyang GAO,Weiwei CHEN,Xinyu MENG,Bingjie CUI,Jing DU. Construction of human lncRNA-GACAT2 over-expression vector and its effect on proliferation and stemness of lung cancer cells [J]. Journal of Jilin University(Medicine Edition), 2023, 49(5): 1147-1153.
[13]	Chang GAO,Yan LIU,Haoxiang YANG,Cuicui ZHANG. Effect of long non-coding RNA MALAT1 on angiogenesis of human brain microvascular endothelial cells induced by oxygen-glucose deprivation/reoxygenation hypoxic [J]. Journal of Jilin University(Medicine Edition), 2023, 49(4): 832-839.
[14]	Shengyu YAN,Changhua LIU,Zhijie XU,Yating DING,Yafeng XIE,Qiao ZHANG,Wanying LIU. Effect of lncRNA PAX8-AS1 on proliferation, apoptosis and invasion of colorectal cancer cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2023, 49(3): 656-664.
[15]	Lingyao XU,Shutang WEI,Yong DONG,Zhenglu SUN,Junbo ZHAO,Dazheng HAN. Regulatory effect of lncRNA MALAT1 on activation of hepatic stellate cell and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2023, 49(3): 697-705.